What are the kids using?Inhalants, CCCs, Dextromethorphan and

other Hallucinogens

Kirk Moberg, MD, PhD, FASAMMedical Director, Illinois Institute for Addiction Recovery

Clinical Professor, Departments of Internal Medicine and Psychiatry and Behavioral Medicine

University of Illinois College of MedicineIllinois Alcohol and other Drug Abuse Professional Certification Association, Inc.

March 17, 2016

Agenda

• Statistics

• Inhalants

• Dissociatives

• Hallucinogens

• Cold remedies

• Miscellaneous

• Synthetic Cannabinoids

STATISTICS

Let’s start with some statistics

Monitoring the Future StudyUniversity of Michigan44,892 students382 public and private schoolsFunding Source: National Institute on Drug Abuse

Prevalence among past year drug use among 12th graders

Drug Prevalence

Alcohol 58.2

Marijuana/Hashish 34.9

Hookah 19.8

Small cigars 15.9

Amphetamines* 7.7

Adderall* 7.5

Snus 5.8

Narcotics o/t Heroin* 5.4

Synthetic Cannabinoids 5.2

Tranquilizers* 4.7

Cough Medicine* 4.6

Vicodin* 4.4

Hallucinogens 4.2

OxyContin* 3.7

Sedatives* 3.6

MDMA (Ecstasy) 3.6

LSD 2.9

Hall other than LSD 2.9

Cocaine (any form) 2.5

Ritalin* 2.0

Inhalants 1.9

Salvia 1.9

* Nonmedical use Categories not mutually exclusive

Tobacco

e-cigarette risk

e-cigarette substance

Tobacco vs. Cannabis

Cannabis

Cannabis

Cannabis Risk

Synthetic Cannabinoids

Prescription Opioids

Prescription Opioids

Heroin

INHALANTS

Inhalants

Inhalants

• Volatile hydrocarbons

– Solvents

– Adhesives

– Paint removers

– Etc.

• Nitrous oxide

• Alkyl nitrites

Three classifications

Aerosol

Volatile hydrocarbons

Gas phase

Volatile hydrocarbons

ButaneEther

Adhesives and thinners

Diflouroethane

Alkyl nitrites

Poppers

Uses: vasodilator (heart disease); cyanide poisoning; euphoria (especially with cocaine and MDMA); enhancesexual experience

Chloroethane

Mechanism of action?

• GABA-A

• NMDA

• Acetyl choline

DISSOCIATIVES

Dissociative drugsNMDA receptor antagonists

The trail to dextromethorphan

Racemethorphan

Dextromethorphan (DXM)

Levomethorphan

AntitussiveDissociative

OpioidAnalgesic

Dextrorphan (DXO)

Dextromethorphan Dextrophan

LevomethorphanLevorphanol

DXO pharmacology

• N-Methyl-D-Aspartate receptor antagonist

• m, k receptor agonist

Nitrous oxide

PhencyclidineSchedule II

OralIntravenousInhalationIntranasal

Clinical Presentation

• Rage• Erythema• Dilated Pupils

• Delusions• Amnesia• Nystagmus• Excitation• Skin Dryness

Receptors

• NMDA receptor antagonist

• Dopamine-2 receptor partial agonist

HALLUCINOGENS

Hallucinogens

MDMA

Salvia divinorum

Dimethyltryptamine (DMT)

Psylocybin

Serotonin receptors

Mescaline3, 4, 5-trimethoxyphenethylamine

PeyoteLophophora williamsii

Results

• Altered thinking

• Altered sense of time and self awareness

• Color brilliance and intensity

• Distortions and kaleidoscope forms

• Flattening of three dimensional objects

Psylocybin

More

• 200 species mushrooms

• Psylocybin Psilocin

• Human usage dates back thousands of years

• Serotonin agonist

Effects

• Euphoria

• Visual hallucinations

• Distorted sense of time

• Changes in perception

Dimethyltryptamine

50 plants4 animals

Hallucinogenic toads

5-methoxy-N, N-dimethyltryptamineBufotenin (N, N,-dimethylserotonin)

Lysergic Acid Diethylamide

Methylenedioxymethamphetamine (MDMA)

• Ecstasy

• XTC

• Adam

• Clarity

• Lover’s speed

• Molly

Two sterioisomers

• (l) isomer

– hallucinogenic

– indirect serotonergic agent

• (d) isomer

– stimulant

– indirect sympathomimetic agent

Molly, Mandy or Ecstasy?

• Mandy = Molly (Mandy is a UK term)

• Molly can be defined in two ways

– MDMA that is “pure”

– Methylone: a synthetic cathinone synthesized in 1996 for use as an antidepressant (b, k MDMA)

Methylone

Structural comparison

MDMA

methamphetamine

Methylone (b, k MDMA)

Pleasurable effects

• Energetic

• Peaceful

• Empathetic

• “Gooey”

• “A six hour orgasm”

NBOMe compoundsSchedule I

PhenylethylamineThe base compound

1st generation

2C-C 2C-B 2C-I

1-(4-chloro-2,5-dimethoxyphenyl)-2-aminoethane

2nd generation

25I-NBOMe

25C-NBOMe

25B-NBOMe

High affinity, high potencyKyriakou et al., 2015.

2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine

Effects5-H2A receptor agonist

• Paranoia

• Confusion

• Syncope

• Vasoconstriction

• Nausea

• Yawning

• Insomnia

• Tachycardia

• Dystonia and clonus

• Seizures

• Shaking

• Scrambled communication

• Tunnel vision

• Time dilation

• Dilated pupils

DEATH…with as little as one drop

Overdose or Trauma

Expert Committee on Drug Dependence, WHO, 2014.DEA, Drug and Chemical Diversion Section, 2013.

Salvia divinorum

salvinorin A

k opioid agonistpartial D2 agonist

Salvia divinorum—pharmacology

• Ingested by – Chewing

– Drinking juice

– Smoking

– Inhaling vapor

• Effects– Hallucinations

– Psychosis

• Duration– Few minutes

Salvia divinorum—legal status

• Federal—Controlled substance act doesn’t apply

• Illegal in many states—Illinois, Minnesota

• Wisconsin—illegal to grow and sell but legal to possess

COLD REMEDIES

Lots to choose from

Dextromethorphan; chlorpheniramine

Dextromethorphan; guaifenesinAcetaminophen; chlorpheniramine;dextromethorphan

Acetaminophen; chlorpheniramine

Acetaminophen; dextromethorphan;doxylamine

Ingredients

• Acetaminophen—analgesic—not mind altering

• Chlorpheniramine—antihistamine—sedative

• Doxylamine—antihistamine—sedative

• Dextromethorphan—antitussive—dissociative

• Guaifenesin—expectorant—sedative

The key?

The key?

Guaifenesin causes nausea

Lots to choose from

Dextromethorphan; chlorpheniramine

Dextromethorphan; guaifenesinAcetaminophen; chlorpheniramine;dextromethorphan

Acetaminophen; chlorpheniramine

Acetaminophen; dextromethorphan;doxylamine

MISCELLANEOUS

Codeine and Promethazine

• Children who are CYP2D6 rapid metabolizersoverdose

• Codeine + promethazine + soda pop and/or Jolly Rancher = “Sizzurp,” “Lean,” “Purple Drank,” “Syrup.”

• Promethazine in opioid addicts

• Mepergan = meperidine + promethazine

Alcohol sanitizer

• Best ethyl alcohol on the market is 70%

• A few comparisons

– Beer—4-5%

– Wine—12-14%

– Vodka, whiskey, gin—45%

But if you want you want to drink it

Add salt

SYNTHETIC CANNABINOIDS

Synthetic cannabinoids

No psychoactive effects

CB reverse agonist

Anti-emetic; analgesic100-800x more potent

Prototype of JWH

Pfizer

Partial agonist

Full agonistWeak metabolite of THC

CB reverse agonist

Raphael Mechoulam—1960sProfessor of Medicinal Chemistry

The Hebrew University

Pfizer—1979

John W. Huffman—1984 Professor Emeritus, Organic Chemistry

Clemson University

Washington PostAugust 9,2015

Alexandros Makriyannis—2001 Director of Center for Drug Discovery,

Northeastern University

Classes

• HU series—Raphael Mechoulam at Hebrew University

• CP series—Charles Pfizer

• JWH series—John W. Huffman

• AM series—Alexandros Makriyannis

Debruyne & Le Boisselier, 2015

Anandamideananda=joy (Sanskrit)

Activates m opioid and GABA receptors which increase dopamine and serotonin

Acetaminophen metabolized to AM404 which is a potent agonist at TRPV1receptor (analgesia); also may act as reuptake inhibitor for anandamide.

JWH-018

Full agonistPotency: 5x THC

2002: circulated as “spice”2008: banned in Germany after discovering the presence of the compound

JWH-073

Partial agonistDiscovered in circulation 4 weeks after JWH-018 ban

HU-210Hebrew University

Difficult to synthesize100-800x as potent as THC

Seely et al., 2012

XLR-11

Cannabis vs. cannabinoids

• Most symptoms similar to cannabis intoxication– Tachycardia– Reddened eyes– Anxiety– Mild sedation– Hallucinations, acute psychosis– Memory deficits

• Symptoms not typically seen after cannabis intoxication—clenbuterol– Seizures – Hypokalemia – Metabolic acidosis – Hypertension (?)– Nausea/vomiting– Coma – Agitation/violent behavior

Seely et al., 2011

Effects increasing in frequency

• Tachycardia followed by bradycardia

• Seizures

• Stroke

• Cardiac toxicity

• Altered mental status

Three demographic groups

• Marijuana smokers

• Occasional drug users seeking to avoid legal consequences

• Drug naïve, curious experimenters

Seely et al., 2012

Black MambaUniversity of Colorado, 2014

Questions?

kirk.moberg@unitypoint.org